Over the past thirty years, solid organ transplantation has become an increasingly viable treatment option for a variety of diseases and conditions. For example, in the United States alone, kidney transplants are now performed at an annual rate of over 9,000, and heart transplants are performed at the rate of over 1,500 per year. However, rejection of the transplanted tissue due to the recipient's normal immune response and transplant-related pathophysiology in the graft tissue continues to be a major hurdle to successful transplantation. In particular, graft tissue quality is a major factor underlying graft rejection. The method of storing a donor organ once removed from the donor greatly impacts.
Typically, once a donor organ is harvested, the organ is preserved by storage in a portable hypothermic container under sterile conditions. Thus, methods to preserve donor tissue integrity have focused primarily on maintenance of properly hypothermic and sterile conditions. However, tissue integrity compromised after harvesting and during storage remains a barrier to improved long-term survival of organ transplants. Even under carefully monitored hypothermic and sterile conditions, ischemia and reperfusion injury negatively impact donor tissue quality. In particular, ischemic damage to the vascular endothelium can result in accelerated graft atherosclerosis, which adversely affects ultimate survival of the graft. In addition, compromised donor tissue contributes to other chronic pathologies in the graft that result in substantial rates of graft loss.
The problem of compromised organ tissue integrity is a major factor contributing to inadequate supplies of organs for transplant. About one in four patients awaiting cardiac transplantation dies while waiting for a suitable donated heart, and similar supply problems plague candidate recipients of other organs. The waits are due in part to insufficient rates of organ donation from potential donors, but also due in part to insufficient progress in developing successful techniques for preserving donated organs beyond very limited time periods after harvesting. Recent advances in immunosuppressive therapy that otherwise after harvesting. Recent advances in immunosuppressive therapy that otherwise have made organ transplantation more feasible have merely exacerbated the problems of organ supply. Thus, a major hurdle in exploiting improved organ transplantation techniques has been the inability to extend safe preservation of donated organs beyond the currently accepted time limit of about four hours. Preservation time limits of a few hours effectively limit the geographic area within which a donated organ can be transported and still be successfully transplanted. Such time limits also make it difficult or impossible to meaningfully evaluate the donated organ before transplant.
Known organ preservation approaches typically include hypothermic arrest and storage in a liquid medium or perfusate, such as known cardioplegic preservation solutions for hypothermic preservation of donated hearts. However, such approaches still do not prevent myocardial damage due to ischemia, reperfusion, fluid and electrolyte imbalances leading to edema, and metabolic exhaustion at the cellular level leading to a degradation of high-energy phosphates, all known to be factors contributing substantially to tissue damage.
To avoid the problems associated with hypothermic arrest and storage, it is known in the art that normothermic preservation eliminates the need to arrest organ function and the need for hypothermic storage, and reduces reperfusion injury and other time dependent tissue injury associated especially with metabolic rundown and depletion of high-energy phosphates. Thus, known methods for extending organ preservation involve attempts to simulate near-normal physiologic conditions, using various approaches. One approach involves harvesting almost all the donor's organs and using the system to perfuse the needed organ under normothermic conditions. However, as an element of routine transplant practice, this approach is limited because of the myriad practical difficulties involved in removing and preserving heart, lungs, liver, pancreas, and kidneys all together and all in functioning condition. Another related approach to achieving extended extracorporeal preservation of a donor organ involves providing continuous sanguineous perfusion, while maintaining the donor organ in the normal functioning state. Thus, known approaches include apparatus, methods and physiologic media that create an extracorporeal circuit for sanguineously perfusing the harvested organ at normothermic temperatures, thus prolonging preservation of the harvested organ for up to about twenty-four hours or longer. However, such approaches remain relatively cumbersome, are relatively costly, are not readily amenable to transport because they involve fairly complex perfusion systems, and have met with limited success.
In the field of surgery, high-energy laser radiation is now well accepted as a surgical tool for cutting, cauterizing, and ablating biological tissue. High-energy lasers are now routinely used for vaporizing superficial skin lesions and, and to make deep cuts. For a laser to be suitable for use as a surgical laser, it must provide light energy at a power sufficient to heat tissue to temperatures over 50 C. Power outputs for surgical lasers vary from 1-5 W for vaporizing superficial tissue, to about 100 W for deep cutting.
In contrast, low level laser therapy involves therapeutic administration of laser energy to a patient at vastly lower power outputs than those used in high energy laser applications, resulting in desirable biostimulatory effects while leaving tissue undamaged. For example, in rat models of myocardial infarction and ischemia-reperfusion injury, low energy laser irradiation reduces infarct size and left ventricular dilation, and enhances angiogenesis in the myocardium. (Yaakobi et al., J. Appl. Physiol. 90, 2411-19 (2001)). Low level laser therapy has been described for treating pain, including headache and muscle pain, and inflammation. The use of low level laser therapy to accelerate bone remodeling and healing of fractures has also been described. (See, e.g., J. Tuner and L. Hode, Low LEVEL LASER THERAPY, Stockholm:Prima Books, 113-16, 1999, which is herein incorporated by reference).
However, known low level laser therapy methods are circumscribed by setting only certain selected parameters within specified limits. For example, known methods are characterized by application of laser energy at a set wavelength using a laser source having a set power output. Specifically, known methods are generally typified by selecting a wavelength of the power source, setting the power output of the laser source at very low levels of 5 mW to 100 mW, setting low dosages of at most about 1-10 Joule/cm2, and setting time periods of application of the laser energy at twenty seconds to minutes. However, other parameters can be varied in the use of low level laser therapy. In particular, known low level laser therapy methods have not addressed the multiple other factors that may contribute to the efficacy of low level laser therapy.
Against this background, a high level of interest remains in finding new and improved methods for preserving harvested organs for transplant thus to extend the time period for preservation. A need thus remains for simple, portable and cost-effective apparatus and methods that provide the ability to extend the organ preservation period beyond accepted limits, while avoiding time-dependent tissue damage due to ischemia and reperfusion, and depletion of high-energy phosphates. A need also remains for apparatus and methods that help to overcome organ transplant rejection, and enhance the survival time of transplanted organs, by improving the tissue quality of transplanted organs.